不同情绪状态与注意缺陷多动障碍关系研究

Relationship between different emotional states and attention-deficit/hyperactivity disorder

摘要

目的 明确注意缺陷多动障碍(ADHD)与多种情绪状态的因果关系及神经解剖学机制,评估前额叶皮层体积的中介作用,为 ADHD 早期干预提供理论支撑。方法 基于2018—2023年公开全基因组关联研究(GWAS)数据,采用双样本双向孟德尔随机化(MR)及中介MR分析,纳入12种情绪状态(GWAS样本量n=380 506)、ADHD(n=225 534)及前额叶皮层体积(n=32 418)的遗传数据,通过逆方差加权(IVW)法、多变量MR+Delta法量化效应,结合多重稳健性检验及年龄分层(儿童6~12岁、青少年13~19岁、成人≥20岁)分析。结果 内疚(OR=2.64,95%CI:1.42~4.91,P=0.002)和厌倦(OR=2.18,95%CI:1.48~3.20,P<0.001)与ADHD呈显著正向因果关联,无反向因果效应;前额叶皮层体积在二者关联中起中介作用,中介比例分别为74.4%和68.3%(P<0.001),且青少年亚组中介效应最强,中介比例分别为83.7%、77.8%(P<0.001)。结论 内疚、厌倦情绪是 ADHD 的潜在上游风险因素,前额叶皮层体积介导二者关联,青少年期为关键敏感阶段。本研究基于欧洲人群遗传数据开展,结论的人群适用性仍需结合不同遗传背景进一步验证,但仍为 ADHD 早期干预提供潜在新靶点。

Abstract

Objective To clarify the causal relationship and neuroanatomical mechanisms between attention-deficit/hyperactivity disorder (ADHD) and various emotional states, and to evaluate the mediating role of prefrontal cortex volume, so as to provide a theoretical basis for early intervention in ADHD. Methods Based on publicly available Genome-Wide Association Study (GWAS) data from 2018 to 2023, two-sample bidirectional Mendelian Randomization (MR) and mediation MR analysis were adopted.The study incorporated genetic data for 12 emotional traits (n=380 506), ADHD (n=225 534), and prefrontal cortex volume (n=32 418).Effects were quantified using the Inverse Variance Weighted (IVW) method and multivariate MR+Delta method, combined with multiple robustness tests and stratified analysis by age (children: 6 - 12 years old, adolescents: 13 - 19 years old, adults: ≥20 years old). Results Guilt (OR=2.64, 95% CI: 1.42 - 4.91, P=0.002) and boredom (OR=2.18, 95% CI: 1.48 - 3.20, P<0.001) exhibited significant positive causal associations with ADHD, with no evidence of reverse causality.Prefrontal cortex volume played a major mediating role in these associations, accounting for 74.4% and 68.3% of the total effect, respectively (P<0.001).Age-stratified analysis indicated that this mediating effect was strongest during adolescence (13 - 19 years), with mediation proportions reaching 83.7% and 77.8% (P<0.001). Conclusions Guilt and boredom are potential upstream risk factors for ADHD, and prefrontal cortex volume mediates the association between these two emotions and ADHD.Although this study is based on genetic data from European populations and its generalizability to diverse genetic backgrounds requires further verification, it identifies potential new targets for early intervention in ADHD.

关键词

情绪 / 注意缺陷多动障碍 / 厌倦 / 内疚 / 前额叶皮层

Key words

emotion / attention-deficit/hyperactivity disorder / boredom / guilt / prefrontal cortex

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基金资助

山东省自然科学基金(ZR2021MH296); 山东省医药卫生科技项目(202412030598); 山东省中医药科技项目(Z20243204)